Gastric cancer is the 4th most common cancer in men worldwide, following lung cancer, prostate cancer, and colorectal cancer and is the 5th most common cancer in women (Non Patent Literature 1). Gastric cancer killed an estimated 464,000 men and an estimated 273,000 women in 2011 (Non Patent Literature 2). There is thus a significant medical need. Gastric cancer is very common in some regions including East Asia, Middle Eastern Europe, and South America and is the highest incidence cancer in men in Japan (Non Patent Literature 3).
Trastuzumab, which is a molecular target drug, was approved by FDA in 2010 based on the clinical trial results for patients with HER2-positive gastric cancer (Non Patent Literature 4). However, the HER2-positive rate was reported to be about 30% in the intestinal type gastric cancer and 10% or lower in the diffuse type gastric cancer (Non Patent Literature 5). Therefore, there is still a significant medical need to treat patients with gastric cancer. VEGF and EGFR are molecules known to be highly expressed in gastric cancer. Bevacizumab, which is an anti-VEGF antibody drug, and Cetuximab, which is an anti-EGFR antibody drug, proceeded to phase 3 clinical trials but both failed to be approved due to insufficient drug efficacy (Non Patent Literatures 6 and 7). This requires development of new drugs.
RHOA, which is a molecule belonging to the RAS small GTPase super family, is known to be highly expressed in cancer sites in a wide variety of cancer types, including breast cancer, colorectal cancer, liver cancer, esophageal cancer, gastric cancer, and lung cancer, at mRNA and protein levels (Non Patent Literatures 8-10). The high expression of RHOA is often reported to be involved in cancer metastasis, including infiltration and migration, rather than carcinogenesis. The high expression of RHOA was observed to contribute to cancer metastasis in experiments using different cancer cell lines including a breast cancer cell line (Non Patent Literature 11).